Composition for external application

ABSTRACT

The present invention relates to a composition for external application, a humectant and a skin barrier function reinforcing agent, each containing a diamide derivative represented by the following formula (1): 
                         
(wherein, R 1a  and R 1b  are the same or different and each represents a C 1-23  hydrocarbon group, R 2a  and R 2b  are the same or different and each represents a divalent C 1-6  hydrocarbon group, R 3 s are the same or different and each represents a divalent C 2-6  hydrocarbon group and n stands for 1 to 100).
 
     The composition for external application, humectant and skin barrier function reinforcing agent basically improve the water retaining ability and barrier functions of the horny layer, are excellent in miscibility and mixing stability and can be prepared efficiently at a low cost.

This is a continuation application of U.S. Ser. No. 10/082,115, filed onFeb. 26, 2002 pending.

TECHNICAL FIELD

The present invention relates to compounds capable of maintaining normalbarrier functions of the horny layer of the skin and improving its waterretaining ability, thereby exhibiting skin roughness lessening effectsand the like, and compositions for external application containing thesecompounds.

BACKGROUND ART

When the water retaining ability or barrier functions of the horny layerare weakened by some internal or external reasons, the skin suffers fromvarious troubles accelerating skin roughness or aging. Lowering in thewater retaining ability and barrier functions of the horny layer canalso be recognized in the roughened skin resulting from various skindiseases such as atopic dermatitis, psoriasis or xeroderma. Therefore,the maintenance • reinforcement of the water retaining ability andbarrier functions of the horny layer are highly important for ourhealthy daily life.

With the foregoing in view, the present applicants found, as adermatologic preparation for external application having effects ofbasically improving (maintaining, reinforcing) the barrier functions ofthe horny layer, dermatologic preparations for external applicationcontaining amide derivatives represented by the below-described formula(2) and applied for a patent (Japanese Patent Laid-Open No. Hei4-12825).

(wherein, R^(a) represents a linear or branched, saturated orunsaturated C₁₀₋₄₀ hydrocarbon group, R^(b) represents a linear orbranched, divalent C₃₋₃₉ hydrocarbon group, and R^(c) represents ahydrogen atom, a linear or branched, saturated or unsaturated C₁₀₋₄₀hydrocarbon group or an acyl group).

Although such amide derivatives bring about excellent effects asdescribed above, their solubility in a base ingredient or stabilitytherewith is not always sufficient. There is therefore a room left forimprovement in miscibility or mixing stability of the derivative to beincorporated in a dermatologic preparation for external application.These amide derivatives are accompanied with another problem thatnecessity of multi-stage reaction upon preparation inevitably leads to arise in the production cost.

An object of the present invention is to provide a composition forexternal application which is capable of basically improving the waterretaining ability and barrier functions of the horny layer, excellent inmiscibility and mixing stability, and available efficiently at a lowcost.

DISCLOSURE OF THE INVENTION

The present inventors have carried out a further investigation on amidederivatives. As a result, it has been found that diamide derivativesrepresented by the below-described formula (1) are effective forreinforcing the water retaining ability of the horny layer and improvingthe barrier functions of it and at the same time, have excellentmiscibility and mixing stability so that they are useful as compositionsfor external application having preventive • remedial effects for skintroubles such as chapping, and hair protective effects.

In the present invention, there are thus provided compositions forexternal application, each containing a diamide derivative representedby the following formula (1):

(wherein, R^(1a) and R^(1b) are the same or different and eachrepresents a C₁₋₂₃ hydrocarbon group, R^(2a) and R^(2b) are the same ordifferent and each represents a divalent C₁₋₆ hydrocarbon group, R³s arethe same or different and each represents a divalent C₂₋₆ hydrocarbongroup and n stands for 1 to 100); compositions for external application,each containing said diamide derivative and an intercellular lipidcomponent of the horny layer; and humectants and skin barrier functionreinforcing agents each having the diamide derivative as an effectiveingredient.

In the present invention, there are also provided a method forreinforcing the water retaining ability of the horny layer and a methodfor reinforcing the skin barrier functions, each comprising applying aneffective amount of said diamide derivative to the skin.

In the present invention, there is also provided a method for relievingexcessive hair dryness or improving the touch feel of the hair, whichcomprising applying an effective amount of said diamide derivative tothe hair.

In the present invention, there is also provided the use of said diamidederivative for the preparation of compositions for external application.

In the present invention, there is also provided a diamide derivativerepresented by the following formula (1′):

(wherein, R^(1a′) and R^(1b′) are the same or different and eachrepresents a branched C₄₋₂₃ hydrocarbon group, R^(2a) and R^(2b) are thesame or different and each represents a divalent C₁₋₆ hydrocarbon group,R³s are the same or different and each represents a divalent C₂₋₆hydrocarbon group and n stands for 1 to 100).

BEST MODE FOR CARRYING OUT THE INVENTION

In the diamide derivative (1) of the present invention, as the C₁₋₂₃hydrocarbon group represented by R^(1a) and R^(1b), preferred are linearor branched C₅₋₁₇ alkyl or alkenyl groups, with the case wherein R^(1a)and R^(1b) represent the same group being more preferred. Particularlypreferred examples of the hydrocarbon group include pentyl, heptyl,nonyl, undecyl, tridecyl, pentadecyl, heptadecyl, 1-ethylheptyl,2,4,4-trimethylpentyl, 1-heptyldecyl, isoheptadecyl, methyl-branchedisoheptadecyl, 8-heptadecenyl and 8,11-heptadecadienyl groups.

The compound represented by the formula (1′) wherein R^(1a) and R^(1b)each represents a branched hydrocarbon group having at least 4 carbonatoms is a novel one.

As the divalent C₁₋₆ hydrocarbon group represented by R^(2a) and R^(2b),linear or branched C₂₋₆ alkylene groups are preferred, with the casewherein R^(2a) and R^(2b) represent the same group being more preferred.Particularly preferred examples of the divalent hydrocarbon groupinclude ethylene, trimethylene, tetramethylene, pentamethylene,hexamethylene, 1-methylethylene and 2-methylethylene groups, of which1-methylethylene and 2-methylethylene groups are more preferred.

As the divalent C₂₋₆ hydrocarbon group represented by R³, linear orbranched C₂₋₆ alkylene groups are preferred. Of these, ethylene,trimethylene, tetramethylene, pentamethylene, hexamethylene,1-methylethylene, 2-methylethylene and 2,2-dimethyltrimethylene groupsare preferred, with ethylene, 1-methylethylene and 2-methylethylenegroups are especially preferred.

Preferably, n stands for 1 to 50, more preferably 1 to 10, with thenumber less than 4 being especially preferred.

As the diamide derivative (1), compounds of the formula (1) having, incombination, the above-exemplified preferred groups as R^(1a), R^(1b),R^(2a), R^(2b), R³ and n, respectively are preferred. Among them,compounds wherein some or all of the hydrocarbon groups as R^(1a),R^(1b), R^(2a), R^(2b) and R³ are branched are preferred to compoundswhose hydrocarbon groups are all linear, because the former ones have alow melting point and therefore have excellent miscibility.

The diamide derivatives (1) to be used for the composition for externalapplication according to the present invention can be prepared by aknown amide synthesizing process. It can be prepared efficiently at alow cost, for example, by the below-described process.

(wherein, R^(1a), R^(1b), R^(2a), R^(2b), R³ and n have the samemeanings as described above).

The target diamide derivative (1) is available efficiently by reactingthe corresponding diamine (3) with a carboxylic acid (4a) and/or (4b) orreaction derivative (ester, acid halide, acid anhydride or the like)thereof.

The reaction is preferably effected at room temperature to 300° C. underreduced pressure of 1.3 Pa to normal pressure in the presence or absenceof a dehydrating agent such as dicyclohexyl carbodiimide or a base, forexample, an alkali metal hydroxide such as potassium hydroxide or sodiumhydroxide, an alkaline earth metal hydroxide such as calcium hydroxide,an alkali metal carbonate such as potassium carbonate, an alkaline earthmetal carbonate such as calcium carbonate, an alkali metal alcoholatesuch as sodium methoxide, sodium ethoxide or potassium-tert-butoxide, ora tertiary amine such as triethylamine or pyridine. Upon this reaction,the carboxylic acid (4a) and/or (4b) or reaction derivative thereof ispreferably used in an excess amount, that is, at least 2 equivalentsrelative to the diamine (3). Reaction while removing the resulting waterout of the system is preferred, because it permits rapid progress of thereaction. The diamide derivative (1) thus available can be purified bythe known method such as washing with water, liquid-liquid extraction,column chromatography, distillation, crystallization, recrystallizationor pulverization.

Examples of the diamine (3) include polyoxyethylene diamine,polyoxypropylene diamine and polyoxyethylene-oxypropylene diamine, morespecifically, polyoxyalkylene diamines “JEFFAMINE” (trade mark, productof HUNTSMAN CORPORATION).

The diamide derivatives (1) of the present invention thus available haveeffects of maintaining and improving the barrier functions of the skinhorny layer and improving water retaining ability of the horny layer sothat they are useful as humectants or skin barrier function reinforcingagents. Compositions for external application containing them areeffective for remedial effects for skin trouble such as chapping.

In the present invention, use in combination with a water solublehumectant selected from polyhydric alcohols, organic acids or saltsthereof, or derivatives thereof and plant extracts makes it possible tosynergistically heighten the water retaining ability of the horny layer.

Examples of the polyhydric alcohol include polyglycerins such asglycerin, diglycerin, triglycerin and tetraglycerin, ethylene glycol,1,3-butylene glycol, 1,4-butylene glycol, propylene glycol, dipropyleneglycol, polyethylene glycol, 1,3-propanediol, glucose, maltose,maltitol, sucrose, fructose, xylitol, sorbitol, maltotriose, threitol,erythritol, starch degraded and reduced alcohol, sorbitol,polyoxyalkylene alkyl glucosides. Of these, glycerin, 1,3-butyleneglycol, propylene glycol and dipropylene glycol are preferred.

Two or more of these polyhydric alcohols may be used in combination.When they are incorporated in the composition of the present inventionfor external application in an amount ranging from 0.001 to 50 wt. %(which will hereinafter be called “%”, simply), preferably from 0.01 to40%, especially from 0.1 to 30%, the water retaining ability of thehorny layer can be heightened synergistically.

Examples of the organic acid and organic acid derivatives include C₂₋₂₈oxycarboxylic acids such as glycolic acid, lactic acid, citric acid and2-hydroxyoctanoic acid, C₂₋₁₂ dicarboxylic acids such as succinic acid,fumaric acid, maleic acid, malonic acid and 1,3-propanedicarboxylicacid, amino acids and derivatives thereof such as aspartic acid,asparagine, glycine, glutamic acid, glutamine, γ-aminobutyric acid,arginine, cysteine and alanine; dicarboxylic monoesters such as octylsuccinate and methyl maleate; nicotinic acid or salts thereof, orderivatives thereof such as nicotinic acid, methyl nicotinate, ethylnicotinate, benzyl nicotinate, nicotinamide, tocopherol nicotinate,quinolinic acid, pyridine-3,5-dicarboxylic acid, nicotinamide adeninedinucleotide phosphate (NADP), nicotinic acid mononucleotide, nicotinylalcohol and nicotinyl alcohol tartrate; and sterine derivativesrepresented by the following formula (5):

[wherein, R⁴ represents —(CH₂)_(l)— (l stands for 2 to 10),

(in which R⁶ represents a linear or branched C₆₋₂₀ alkyl or alkenylgroup), and R⁵ represents natural sterine or a residue obtained byremoving a hydroxyl group proton from the hydrogenated product of thenatural sterine].

As the sterine derivative, those of the formula (5) wherein l stands for2 to 5, R⁶ represents hexadecenyl or octadecenyl and R⁵ representscholesteryl or sitosteryl are preferred.

As the organic acid or organic acid derivative, preferred areα-hydroxycarboxylic acid, amino acid and nicotinic acid and derivativesthereof, with glycolic acid, lactic acid, citric acid, succinic acid,aspartic acid, glycine, arginine, nicotinamide, tocopherol nicotinateand glycine betaine being especially preferred.

Examples of the salt of the organic acid include potassium salt,magnesium salt, calcium salt, aluminum salt and basic amino acid saltsof lactic acid, citric acid and succinic acid. When the organic acid hasa basic group, examples include acid addition salts of hydrochloricacid, sulfuric acid, nitric acid and phosphoric acid.

At least two of these organic acids or salts thereof, or derivativesthereof may be used in combination. They are preferably incorporated inthe invention composition for external application in an amount of0.0001 to 10%, especially 0.001 to 5%.

As the plant extract, those described in Japanese Patent Laid-Open No.Hei 9-165313 can be mentioned as examples. Of these, especiallypreferred are extracts, steam distillates or compressed products ofeucalyptus, hops, ginger, balloonflower, GANPIRUNOKI, wild rose,angelica, lily, adlay, cattail, loquat, gardenia, ginseng, soapwort,birch, hydrangea, cloves, safflower, burnet, iris or Sophoraflavewscens. As an extracting solvent, water, ethanol, 1,3-butyleneglycol or the like is usable.

Two or more of these plant extracts may be used in combination. They arepreferably incorporated in the composition of the present invention inan amount of 0.0001 to 10%, especially 0.0001 to 5% in terms of a drysolid content.

In the present invention, use in combination of an intercellular lipidcomponent of the horny layer selected from ceramides, pseudoceramides,sphingoglycolipids, sphingophospholipids, sphingosines and derivativesthereof, sphinganines and derivatives thereof, higher fatty acids,cholesterols and derivatives thereof makes it possible tosynergistically heighten the barrier functions of the horny layer.

The ceramides include natural ceramides extracted from the brain orskin, followed by purification and synthetic ceramides synthesized bythe microbiological or chemical method.

Examples of the natural ceramide include ceramides of Types I to VII,N-oleoyl-sphingosine, N-(12-hydroxyoctadecanoyl)sphingosine,N-(16-hydroxyhexadecanoyl)sphingosine and bovine brain ceramide.

As the synthesizing method of a synthetic ceramide, that described, forexample, in Japanese Patent Laid-Open No. Sho 59-7118, Japanese PatentLaid-Open No. Hei 4-342553 or WO93/22281 can be employed.

Pseudoceramides can be prepared in accordance with the method described,for example, in Japanese Patent Laid-Open No. Sho 62-228048 or JapanesePatent Laid-Open No. Sho 63-216852. Particularly preferred examples ofthe pseudoceramide include compounds represented by the followingformula (6):

(wherein, R⁷ represents a C₉₋₁₇ alkyl group and R⁸ represents a C₁₀₋₁₈alkyl group).

Similar to the above-described ceramides, sphingoglycolipids andsphingophospholipids include natural and synthetic ones. Examples of thesphingoglycolipids include those having, as a constituent sugar,glucose, mannose, galactose, glucuronic acid and glucosamine. They alsoinclude selebroside and sulfate esters thereof. As thesphingophospholipids, sphingomyelin can be exemplified.

As the sphingosines preferably used in combination, as well asceramides, pseudoceramides, sphingoglycolipids and sphingophospholipids,preferred are sphingosines disclosed in Japanese Patent Laid-Open No.Hei 5-85924, compounds disclosed in Japanese Patent Laid-Open No. Hei6-271446 and represented by the formula (7), compounds disclosed inJapanese Patent Laid-Open No. Hei 5-194185 and represented by theformula (8).

Examples of the sphingosines disclosed in Japanese Patent Laid-Open No.Hei 5-85924 include sphingosine (sphingenine), dihydrosphingosine(sphinganine), phytosphingosine, dehydrosphingosine,dehydrophytosphingosine, and sphingadienine and N-methyl derivatives orN,N-dimethyl derivatives thereof. The hydrocarbon group of thesecompounds preferably has 12 to 24 carbon atoms and it may be eitherlinear or branched, and either saturated or unsaturated.

The compound (7) disclosed in Japanese Patent Laid-Open No. Hei 6-271446is represented by the following formula:

(wherein, R⁹ represents a C₁₋₄₀ hydrocarbon group which may have ahydroxyl group, Z represents —CH₂OH, —CO₂H or

and W represents —NH₂, —NHCH₃, —N(CH₃)₂ or —N⁺(CH₃)₃).

The compound (8) disclosed in Japanese Patent Laid-Open No. Hei 5-194185is represented by the following formula:

(wherein, R¹⁰ represents a linear, branched or cyclic, saturated orunsaturated C₄₋₄₀ hydrocarbon group, R¹¹, R¹², R¹³, R¹⁴ and R¹⁵ eachindependently represents a hydrogen atom or a C₁₋₁₀ hydrocarbon groupwhich may be substituted by at least one hydroxyl group).

As the higher fatty acid, those having 12 or more carbon atoms arepreferred, with those having 12 to 24 carbon atoms being especiallypreferred. Specific examples include myristic acid, palmitic acid,palmitoleic acid, stearic acid, oleic acid, linoleic acid and behenicacid. Monoglycerides, diglycerides or triglycerides rich in such ahigher fatty acid may be incorporated.

As the cholesterol ester, those composed of a higher fatty acid having12 or more carbon atoms, especially 12 to 24 carbon atoms are preferred.Specific examples include cholesteryl palmitate, cholesterylisostearate, di(cholesterol, 2-octyldodecyl) N-lauroyl-L-glutamate,lanoline fatty acid cholesterol and macadamia nut oil fatty acidcholesterol.

Two or more of these intercellular lipid components of the horny layermay be used in combination. They may be incorporated in the compositionof the present invention preferably in an amount of 0.001 to 20%,especially 0.005 to 10%.

The content of the diamide derivative (1) in the composition of thepresent invention is preferably 0.001 to 50% of the whole compositionwhen the composition is an emulsion type dermatologic preparation fortopical application. It is preferably 0.01 to 50% of the wholecomposition when the composition is an oily type dermatologic externalpreparation containing a liquid hydrocarbon such as squalane as a baseingredient. In either case, addition of it in an amount of 0.01 to 20%is especially preferred. Particularly for the prevention or remedy ofskin roughness, addition of it in an amount of 0.1 to 20% is preferred.

The composition for external application according to the presentinvention can be classified roughly, from the viewpoint of its type ofusage, into a medicinal dermatologic external preparation and a cosmeticcomposition. It is preferred to use as a cosmetic composition, inparticular as a cosmetics for skin.

As the medicinal dermatologic external preparation, various ointmentscontaining a pharmaceutically effective ingredient can be mentioned byway of example. As the ointment, either one of an ointment having anoily base or a water-in-oil or an ointment having an oil-in-wateremulsion base can be used. Examples of the oily base include vegetableoils, animal oils, synthetic oils, fatty acids, natural and syntheticglycerides and the like. As the pharmaceutically effective ingredient,an analgesic anti-inflammatory agent, antipruritic, disinfectantantiseptic, astringent, skin softening agent, hormone or the like can beused, for example, as needed.

When used as a cosmetic composition (including skin cosmetic compositionand hair cosmetic composition), on the other hand, generally-employedcosmetic ingredients such as oily ingredient, surfactant, humectant,ultraviolet absorber, whitening agent, wrinkle remedy, alcohol,chelating agent, pH regulator, antiseptic, thickener, colorant andperfume can be added in any combination to the diamide derivative (1)which is an essential ingredient.

As a cosmetic composition, it is possible to use it in various formssuch as water-in-oil or oil-in-water emulsified cosmetic composition,cream, milky lotion, skin lotion, oily cosmetic composition, lip stick,foundation, bath agent, skin cleanser, nail care agent, and haircosmetic compositions. Specific examples of the hair cosmeticcompositions include hair tonic, hair dressing, hair rinse, hairtreatment, hair conditioner, hair styling agent, shampoo, baldnessremedy and hair growth accelerator.

In the medicinal dermatologic external composition or skin cosmeticcomposition among the compositions for external application according tothe present invention, surfactants such as anionic surfactants, cationicsurfactants, nonionic surfactants and amphoteric surfactants can beincorporated. Of these, nonionic surfactants such as polyoxyethylenealkyl ethers, polyoxyethylene fatty acid esters, sorbitan fatty acidesters, polyoxyethylene sorbitan fatty acid esters, fatty acidmonoglycerides and glyceryl ether are preferred. The surfactant ispreferably added in an amount of 0.01 to 20%, especially 0.1 to 10%,based on the composition.

When the composition of the present invention is used as a hair cosmeticcomposition, the diamide derivative (1) is preferably added in an amountof 0.001 to 5% for shampoo or the like, 0.1 to 20% for rinse, treatment,conditioner, styling agent or the like, and 0.01 to 5% for hair liquid,hair tonic or the like.

In the hair cosmetic composition, surfactants such as anionicsurfactants, cationic surfactants, nonionic surfactants and amphotericsurfactants and ingredients ordinarily employed for hair cosmeticcompositions can be incorporated. When the hair cosmetic composition isa shampoo, an anionic surfactant such as alkyl ether sulfate, alkylsulfate or olefin sulfonate salt can be incorporated as a mainsurfactant. Its content is preferably 5 to 30% in the composition, with10 to 20% being especially preferred.

When the cosmetic composition of the present invention is a hair rinse,conditioner, hair treatment or hair styling agent, a cationic surfactantsuch as mono- or di-(longer chain)alkyl quaternary ammonium salt, anonionic surfactant such as polyoxyethylene alkyl or alkenyl ether, oran oil or fat such as liquid paraffin can be incorporated in order toimpart the hair with good touch feel. The cationic and nonionicsurfactants are preferably added in an amount of 0.1 to 50%, especially0.5 to 20% in the composition.

When the hair cosmetic composition is a hair liquid, hair tonic or thelike, a nonionic surfactant such as polyoxyethylene can be incorporatedin it. The nonionic surfactant is preferably added in an amount of 0.01to 20%, especially 0.1 to 5% in the whole composition.

EXAMPLES Preparation Example 1

Preparation of Compound (A)

In a flask equipped with a stirrer, a nitrogen inlet tube and adistillation apparatus, 317 g of caprylic acid (“LUNAC 8-98(E)”, productof Kao Corp.) was charged, followed by dropwise addition of 228 g of“JEFFAMINE D-230” (product of Huntsman Corp.) over 2.5 hours at 220° C.under stirring in a nitrogen gas stream. Under the same conditions, thereaction mixture was matured for 5 hours. The dropwise addition andmaturation were conducted under a nitrogen gas stream, made it possibleto conduct them while distilling off the water byproduced. Aftercompletion of the reaction, the reaction mixture was subjected tomolecular distillation (160 to 210° C., 0.5 Pa), whereby 262 g of thetitle compound (A) was obtained. The resulting Compound (A) has physicalproperties as follows:

Colorless Oil

¹H-NMR (CDCl₃, δ): 0.80-1.00 (m), 1.00-1.50 (m), 1.50-1.80 (m), 2.13(t,J=7.5 Hz), 3.00-3.75 (m), 4.00-4.30 (m), 5.60-6.10 (m).

Preparation Examples 2 to 11

In a similar manner to Preparation Example 1 except for the use of thecompounds shown in Table 1 instead of Diamine (3) and Carboxylic acid(4a) or (4b), the below-described Compounds (B)-(k) were prepared. Thephysical properties of each of the diamide derivatives are also shown inTable 1 and Table 2.

TABLE 1 Diamide Carboxylic acid derivative (1) Diamine (3) (4a or 4b)Physical properties Prep. Compound (B) JEFFAMINE D-230 Lauric acid Whitesolid, melting point: 74° C. Ex. 2 ¹H-NMR(CDCl₃, δ): 0.80- 1.00(m),1.00- 1.50 (m), 1.50- 1.80(m), 2.13(t, J=7.5Hz), 3.00- 3.75(m), 4.00-4.30(m), 5.60- 6.10(m) Prep. Compound (C) JEFFAMINE D-2302-Ethylhexanoic Colorless oil Ex. 3 acid ¹H-NMR(CDCl₃, δ): 0.80-10.5(m), 1.05- 1.75 (m), 1.75- 2.20(m), 3.30- 3.75(m), 4.10- 4.30(m),5.50- 6.00(m). Prep. Compound (D) JEFFAMINE D-230 3,5,5- Colorless oilEx. 4 Trimethylhexanoic ¹H-NMR(CDCl₃, δ): 0.88(s), acid 0.94(d,J=6.2Hz), 1.00- 1.35(m), 1.85- 2.25 (m), 3.30- 3.70(m), 4.00- 4.30(m),5.50- 6.20(m). Prep. Compound (E) JEFFAMINE XFJ-511 Octanoic acidColorless oil Ex. 5 (polyoxyethylene- ¹H-NMR(CDCl₃, δ): 0.75- 1.00(m),1.00- 1.45 oxypropylene (m), 1.45- 1.75(m), 2.11(t, J=7.6Hz), diamine,product of 3.35- 3.75(m) 3.42(d, J=4.3Hz), 4.00- 4.30 HUNTSMAN CORP)(m), 5.60- 6.30(m). Prep. Compound (F) JEFFAMINE XFJ-511 Lauric acidWhite solid, Melting point: 61° C. Ex. 6 ¹H-NMR(CDCl₃, δ): 0.75-1.00(m), 1.00- 1.45 (m), 1.45- 1.75(m), 2.14(t, J=7.6Hz), 3.40- 3.70(m),3.42(d, J=4.3Hz), 4.00- 4.30 (m), 5.60- 6.20(m). Prep. Compound (G)JEFFAMINE XFJ-511 2-Ethylhexanoic Colorless oil Ex. 7 acid ¹H-NMR(CDCl₃,δ): 0.75- 1.00(m), 1.00- 1.75 (m), 1.75- 2.00(m), 3.40- 3.70(m), 3.40(d,J=4.4Hz), 4.05- 4.35(m), 5.50- 6.20 (m). Prep. Compound (H) JEFFAMINEXFJ-511 3,5,5- Colorless oil Ex. 8 Trimethylhexanoic ¹H-NMR(CDCl₃, δ):0.87(s), acid 0.93(d, J=6.4HZ), 1.00- 1.35(m), 1.80- 2.25 (m), 3.42(d,J=4.3Hz), 3.50- 3.70(m), 4.00- 4.30(m), 5.55- 6.25(m).

TABLE 2 Diamide Carboxylic acid derivative (1) Diamine (3) (4a or 4b)Physical properties Prep. Compound (I) JEFFAMINE EDR- Lauric acid Whitesolid, melting point: 116° C. Ex. 9 148 (polyoxyethylene ¹H-NMR(CDCl₃,δ): 0.85(t, J=6.4H, 6H), diamine; product of 1.10- 1.40(m, 32H), 1.50-1.70(m, 4H), HUNTSMAN CORP) 2.15(t, J=7.6Hz, 4H), 3.45(t, J=5.3Hz, 4H),3.50- 3.65(m, 4H), 3.59(s, 4H), 5.80- 6.00 (m, 2H). Prep. Compound (J)JEFFAMINE EDR- 2-Ethylhexanoic White solid, melting point: 91° C. Ex. 10148 acid ¹H-NMR(CDCl₃, δ): 0.75- 1.05(m, 12H), 1.10- 1.75(m, 16H), 1.75-2.05(m, 2H), 3.40- 3.65 (m, 8H), 3.59(s, 4H), 5.80- 6.00(m, 2H) Prep.Compound (K) JEFFAMINE EDR- 3,5,5- Colorless oil Ex. 11 148Trimethylhexanoic ¹H-NMR(CDCl₃, δ): 0.87(s, 12H), acid 0.93(d, J=6.3Hz,6H), 1.06(dd, J=6.1, 14.0Hz, 2H), 1.21(dd, J=3.6, 14.0Hz, 2H), 1.90(dd,J=7.5, 12.2Hz, 2H), 1.95- 2.15(m, 2H), 2.17(dd, J=5.1H, 14.0Hz, 2H),3.40- 3.65 (m, 8H), 3.58(s, 4H), 5.85- 6.00(m, 2H)Test 1

Compositions for external application according to the present invention(invention products) containing the diamide derivatives prepared inPreparation Examples 1 to 11 and having the compositions as shown inTables 3 to 5 were prepared and their percutaneous water transpirationamount and percutaneous absorption amount were measured and evaluated bythe methods described below.

(Testing Method)

Male Wister rats were raised using only feed free of essential fattyacids. Those rats showing symptoms of essential fatty acid deficiencywere used for the test. After the back of each rat suffering from theessential fatty acid deficiency was shaved thoroughly, the compositionfor external application was applied to the shaved part once a day for12 days. A group consisting of five rats was tested for each compositionto be evaluated. Three days after completion of the application, thebelow-described items of the compositions were measured and evaluated.

(1) Percutaneous Water Transpiration

The water transpiration amount from the skin of the back of each rat wasmeasured by TEVAMETER, and inhibitory effects on percutaneous watertranspiration were found by the below-described formula:Degree of percutaneous water transpiration inhibition by the inventionproduct=Percutaneous water transpiration amount of the rat to whichComparative Product 1 has been applied−percutaneous water transpirationamount of the rat to which the invention product has been applied(g/m²/hr).(2) Percutaneous Absorption

The dorsal skin of the test rat was cut off and fixed on a percutaneousabsorption chamber with the epidermis side up. The lower receiver wasfilled with a phosphate buffer solution. Onto the epidermis, a phosphatebuffer solution containing ¹⁴C-salicylic acid of 37 KBq was added, whichwas then allowed to stand. Nineteen hours later, a fixed amount of thephosphate buffer solution was drawn from the lower receiver and theradioactivity of the ¹⁴C-salicylic acid penetrated into the solution wasmeasured. In accordance with the below-described formula, percutaneousabsorption inhibitory effects were determined.Degree of percutaneous absorption inhibition of the inventionproduct=percutaneous absorption amount of the rat to which ComparativeProduct 1 has been applied−percutaneous absorption amount of the rat towhich the invention product has been applied (dpm)

TABLE 3 Invention Invention Invention Invention Composition (%) product1 product 2 product 3 product 4 Compound (A) 10 — — — Compound (B) — 10— — Compound (C) — — 10 — Compound (D) — — — 10 1,3-Butylene glycol 62.962.9 62.9 62.9 Ethanol 27 27 27 27 Isostearyl glyceryl ether 0.1 0.1 0.10.1

TABLE 4 Invention Invention Invention Invention Composition (%) product5 product 6 product 7 product 8 Compound (E) 10 — — — Compound (F) — 10— — Compound (G) — — 10 — Compound (H) — — — 10 1,3-Butylene glycol 62.962.9 62.9 62.9 Ethanol 27 27 27 27 Isostearyl glyceryl ether 0.1 0.1 0.10.1

TABLE 5 Invention Invention Invention Comparative Composition (%)product 9 product 10 product 11 product 1 Compound (I) 10 — — — Compound(J) — 10 — — Compound (K) — — 10 — 1,3-Butylene glycol 62.9 62.9 62.962.9 Ethanol 27 27 27 30 Isostearyl 0.1 0.1 0.1 0.1 glyceryl ether

TABLE 6 Percutaneous water Percutaneous transpiration absorptioninhibition degree inhibition degree Invention product 1 1.5 2563Invention product 2 1.3 1564 Invention product 3 1.8 2706 Inventionproduct 4 1.3 2890 Invention product 5 1.4 1363 Invention product 6 1.21731 Invention product 7 1.4 1184 Invention product 8 1.1 1088 Inventionproduct 9 0.3 532 Invention product 10 0.8 516 Invention product 11 0.9739

It has been found that the invention products 1 to 11 are superior toComparative product 1 in effects of inhibiting percutaneous watertranspiration and percutaneous absorption and also superior in skinroughness lessening effects.

Test 2

Compositions for external application according to the present invention(invention products) containing the diamide derivative and having thecomposition as shown in Tables 7 and 8 were prepared and theirpercutaneous water transpiration and skin conductance were measured andevaluated by the below-described methods. For comparison, a compositionfor external application (Comparative Product 2) containing Vaseline,which is known to have high skin occlusive property and is thereforeused for external dermatological preparations for medical use or skincosmetic compositions, was subjected to similar measurement andevaluation. Results are shown in Table 9.

(Testing Method)

Ten normal volunteers were washed at the inside of the forearms (botharms), followed by acetone/ether (1/1) treatment to remove theintercellular lipid of the horny layer to roughen their skin. Thecomposition for external application was applied to the test site twicea day for three days. On the next day after final application, the sitewas washed. After rest for 20 minutes at room temperature of 20° C. andhumidity of 30%, the below-described items were measured and evaluated.

(2) Percutaneous Water Transpiration

The percutaneous water transpiration amount was measured by TEVAMETER.In accordance with the below-described formula, effects for inhibitingpercutaneous water transpiration were determined.Degree of percutaneous water transpiration inhibition by the inventionproduct=percutaneous water transpiration amount of the site to which thebase ingredient has been applied−percutaneous water transpiration amountof the site to which the invention product has been applied (g/m²/hr)(2) Water Content in the Horny Layer

The water content in the horny layer was measured by a skin conductancemeter. The higher the conductance, the greater the water content in thehorny layer. In accordance with the below-described formula, effects forimproving water retaining ability of the horny layer were determined.Water retaining ability improving degree of the inventionproduct=conductance of the site to which the invention product has beenapplied−conductance of the site to which the base ingredient has beenapplied (μS)

TABLE 7 Invention Invention Invention Invention Composition (%) product12 product 13 product 14 product 15 Compound (A) 5 — Compound (C) — 5 —— Compound (D) — — 5 — Compound (E) — — — 5 Squalane 2 2 2 2 Neopentylglycol 3 3 3 3 dicaprate Cetanol 3 3 3 3 Stearyl alcohol 2 2 2 2Polyoxyethylene 1 1 1 1 hydrogenated castor oil (40E.O.) Polyoxyethylenesorbitan 0.5 0.5 0.5 0.5 monostearate (20E.O.) Sorbitan monostearate 2.52.5 2.5 2.5 Methyl paraoxybenzoate 0.3 0.3 0.3 0.3 Water Balance BalanceBalance Balance

TABLE 8 Invention Invention Comparative Composition (%) product 16product 17 Product 2 Compound (G) 5 — Compound (K) — 5 — Vaseline — — 5Squalane 2 2 2 Neopentyl glycol 3 3 3 dicaprate Cetanol 3 3 3 Stearylalcohol 2 2 2 Polyoxyethylene 1 1 1 hydrogenated castor oil (40E.O.)Polyoxyethylene 0.5 0.5 0.5 sorbitan monostearate (20E.O.) Sorbitan 2.52.5 2.5 monostearate Methyl 0.3 0.3 0.3 paraoxybenzoate Water BalanceBalance Balance

TABLE 9 Inhibition degree Water of percutaneous retaining ability watertranspiration improving degree Invention product 12 2.2 4.7 Inventionproduct 13 2.8 5.6 Invention product 14 2.1 4.0 Invention product 15 2.25.2 Invention product 16 2.0 4.1 Invention product 17 1.3 3.7Comparative Product 2 0.6 0.1

It has been found that the invention products 12 to 17 were superior tothe comparative product 2 in effects for increasing the water content inthe horny layer, percutaneous water transpiration inhibiting effects andskin roughness remedial effects.

Test 3

Compositions for external application according to the present invention(invention products) having the compositions shown in Tables 10 to 12were prepared and their percutaneous water transpiration, skinconductance and skin roughness were evaluated. For comparison, aVaseline-containing composition for external application (comparativeproduct 2) was subjected the similar evaluation. Results are shown inTables 11 and 13.

(Testing Method)

(1) Percutaneous Water Transpiration

It was evaluated in a similar manner to Test 2.

(2) Water Content in the Horny Layer

It was evaluated in a similar manner to Test 2.

(3) Score of Skin Roughness

Skin roughness was visually observed and ranked in accordance with thebelow-described standards. The score was indicated by an average value.

-   0: No skin roughness is observed.-   1: Slight skin roughness is observed.-   2: Skin roughness is observed.-   3: Rather severe skin roughness is observed.

TABLE 10 Comp. Invention Products Product 2 13 18 19 20 21 22 23 24 2526 2 Diamide compound (C) 5 5 5 5 5 5 5 5 5 5 — Ceramide II (product of— 0.5 — — — 0.5 0.5 0.5 0.5 0.5 — sederma) Ceramide III (product of — —0.5 — — — — — — — — cosmoferm) Sofcareceramide — — — 0.5 — — — — — — —Kao (Jap. Pat. Laid- Open No. Sho 62- 228048) Sphingoglycolipid — — — —0.5 — — — — — — (Kibun Food Chemifa Co., Ltd.) Phytosphingosine — — — —— 0.5 — — — — — Palmitic acid — — — — — — 0.5 — — — — Sunflower oil — —— — — — — 0.5 — — — Cholesterol — — — — — — — — 0.5 — — Cholesterylisostearate — — — — — — — — — 0.5 — Vaseline — — — — — — — — — — 5Squalane 2 2 2 2 2 — 2 2 2 2 2 Neopentyl glycol 3 3 3 3 3 3 3 3 3 3 3dicaprate Cetanol 3 3 3 3 3 3 3 3 3 3 3 Stearyl alcohol 2 2 2 2 2 2 2 22 2 2 Polyoxyethylene 1 1 1 1 1 1 1 1 1 1 1 hydrogenated castor oil(40E.O.) Polyoxyethylene 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5sorbitan monostearate (20E.O.) Sorbitan monostearate 2.5 2.5 2.5 2.5 2.52.5 2.5 2.5 2.5 2.5 2.5 Methyl paraoxybenzoate 0.3 0.3 0.3 0.3 0.3 0.30.3 0.3 0.3 0.3 0.3 Water Balance Balance Balance Balance BalanceBalance Balance Balance Balance Balance Balance

TABLE 11 Inhibition degree Score of percutaneous of skin watertranspiration roughness Invention product 13 2.8 1.6 Invention product18 3.3 1.2 Invention product 19 3.2 1.3 Invention product 20 3.4 1.1Invention product 21 2.9 1.6 Invention product 22 4.5 0.3 Inventionproduct 23 3.9 0.5 Invention product 24 3.5 0.9 Invention product 25 4.20.4 Invention product 26 4.1 0.4 Comparative product 2 0.6 2.7

The invention products 13 and 18 to 26 were superior to ComparativeProduct 2 in effects for inhibiting percutaneous water transpirationfrom the horny layer and skin roughness remedial effects.

TABLE 12 Comp. Invention products Product 13 27 28 29 30 31 32 33 2Diamide compound (C) 5 5 5 5 5 5 5 5 — Glycerin — 0.5 — — — — — — —1,3-Butylene glycol — — 0.5 — — — — — — Eucalyptus extract — — — 0.5 — —— — — (Ichimaru Pharcos Co., Ltd.) Ginger extract (Maruzen — — — — 0.5 —— — — Pharmaceuticals Co., Ltd.) Sodium lactate — — — — — 0.5 — — —Sodium aspartate — — — — — — 0.5 — — Trimethylglycine — — — — — — — 0.5— Vaseline — — — — — — — — 5 Squalane 2 2 2 2 2 2 2 2 2 Neopentyl glycol3 3 3 3 3 3 3 3 3 dicaprate Cetanol 3 3 3 3 3 3 3 3 3 Stearyl alcohol 22 2 2 2 2 2 2 2 Polyoxyethylene 1 1 1 1 1 1 1 1 1 hydrogenated castoroil (40E.O.) Polyoxyethylene 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5sorbitan monostearate (20E.O.) Sorbitan monostearate 2.5 2.5 2.5 2.5 2.52.5 2.5 2.5 2.5 Methyl paraoxybenzoate 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.30.3 Water Balance Balance Balance Balance Balance Balance BalanceBalance Balance

TABLE 13 Water retaining ability improving Score of skin degreeroughness Invention product 13 5.6 1.6 Invention product 27 7.0 1.3Invention product 28 6.1 1.4 Invention product 29 8.8 0.7 Inventionproduct 30 8.5 0.7 Invention product 31 7.9 1.0 Invention product 32 7.51.1 Invention product 33 8.1 0.9 Comparative product 2 0.1 2.7

The invention products 13 and 27 to 33 were superior to ComparativeProduct 2 in effects for increasing the water content in the horny layerand skin roughness remedial effects.

Test 4

Hair rinses of the present invention (invention products) containing thediamide derivatives and having the compositions as listed in Tables 14and 15 were prepared and excessive dryness and touch feel of the hairafter treated with the resulting hair rinses were evaluated by a panelof 5 experts in accordance with the below-described criteria. Theresults are shown in Tables 16 and 17.

-   −2: Bad-   −1: slightly bad-   0: neither good nor bad-   +1: Slightly good-   +2: Good

TABLE 14 Invention product Invention Invention Composition (%) 34Product 35 Product 36 Distearyl dimethylammonium 2 2 2 chloridePropylene glycol 3 3 3 Compound (A) 1 — — Compound (C) — 1 — Compound(D) — — 1 Water Balance Balance Balance

TABLE 15 Invention Invention Comparative Composition (%) product 37Product 38 Product 3 Distearyl dimethylammonium 2 2 2 chloride Propyleneglycol 3 3 3 Compound (E) 1 — — Compound (G) — 1 — Water Balance BalanceBalance

TABLE 16 Invention Invention Invention Evaluation items product 34product 35 product 36 Excessive dryness of the hair +1.8 +1.8 +1.2Favorable touch feel +1.6 +2.0 +1.6

TABLE 17 Invention Invention Comparative Evaluation items product 37product 38 Product 3 Excessive dryness of the hair +1.6 +1.6 −1.2Favorable touch feel +1.6 +1.8 −1.0

The invention products 34 to 38 were superior to Comparative product 3in the effects of alleviating excessive hair dryness and improving thetouch feel of the hair.

Example 1

A skin lotion having the composition shown in Table 18 was prepared in aconventional manner. The resulting hair lotion exhibited excellenteffects for preventing or remedying skin roughness. Compounds (A), (C),(D), (E), (G) and (K) were excellent in miscibility and mixingstability.

TABLE 18 (Composition) (%) Compound (A), (C), (D), (E), (G) or (K) 1.0Glycerin monostearate 1.0 Propylene glycol 4.0 Isopropyl palmitate 3.0Lanolin 1.0 Methyl paraoxybenzoate 0.1 Perfume Trace Colorant TraceWater Balance

Example 2

An O/W cream having the composition shown in Table 19 was prepared in aconventional manner. The resulting O/W cream exhibited excellent effectsfor preventing or remedying skin roughness. Compounds (A), (C), (D),(E), (G) and (K) were excellent in miscibility and mixing stability.

TABLE 19 (Composition) (%) Compound (A), (C), (D), (E), (G) or (K) 3.5Squalane 2.0 Neopentyl glycol dicaprate 3.0 Cetostearyl alcohol 3.0Polyoxyethylene sorbitan monostearate (20E.O.) 2.1 Sorbitan monostearate0.9 Polyoxyethylene hydrogenated castor oil (40E.O.) 1.0 Isostearylglyceryl ether 0.2 Ceramide 2 0.5 86% Glycerin 5.0 Methylparaoxybenzoate 0.3 Water Balance

Example 3

A shampoo having the composition as shown in Table 20 was prepared in aconventional manner. This shampoo improved the touch feel of the hairand prevented • remedied the roughened skin of the scalp. Compound (A),(C), (D), (E), (G) and (K) were excellent in miscibility and mixingstability.

TABLE 20 (Composition) (%) Polyoxyethylene (25) lauryl ether sulfatesodium salt 15.0 Coconut oil fatty acid diethanolamide 3.0 Compound (A),(C), (D), (E), (G) or (K) 2.0 Perfume 0.5 Colorant Trace Citric acidTrace Water Balance

Example 4

A hair liquid composition having the composition shown in Table 21 wasprepared in a conventional manner. The resulting hair liquid compositionimparted the hair with excellent style retention and manageability andgood touch feel. Compounds (A), (C), (D), (E), (G) and (K) wereexcellent in miscibility and mixing stability.

TABLE 21 (Composition) (%) Compound (A), (C), (D), (E), (G) or (K) 1.0Polyoxypropylene (30) butyl ether 15.0 Ethanol 40.0 Water BalancePerfume 0.3

Example 5

A night cream having the composition as described below was prepared.The resulting night cream was effective for recovering a deteriorationin the barrier functions of the skin horny layer and reinforcing thefunctions, heightened the water retaining ability of the horny layer andexhibited skin roughness preventive • remedial effects. Compounds (A),(C), (D), (E), (G) and (K) were excellent in miscibility and mixingstability.

TABLE 22 (Composition) (%) Diamide compound (A), (C), (D), (E), (G) or(K) 10.0 Ceramide 2 (Takasago International Corp.) 1.0 Bovine brainlipid (Q.P. Corp.) 0.5 Sofcare ceramide SLE (Kao Corp.) 3.0 Macadamianut oil fatty acid cholesterol (Nippon Fine 2.0 Chemical Co., Ltd.)Dimethylpolysiloxane 10 cSt 5.0 Polyether-modified silicone 2.0Polyoxyethylene hydrogenated castor oil 1.0 Cyclic silicone 7.0 Glycerin5.0 Magnesium sulfate 0.5 Nicotinic amide 0.2 Dipotassiumglycyrrhizinate 0.1 Amur cork tree extract (Ichimaru Pharcos Co., Ltd.)0.1 Heavy liquid isoparaffin 0.5 Polyvinyl alcohol 0.3 Methylparaoxybenzoate q.s. Perfume q.s. Purified water Balance

Example 6

A sunscreen emulsion having the below-described composition wasprepared. The sunscreen emulsion thus obtained was effective forrecovering a deterioration in barrier functions of the skin horny layerand reinforcing the function, heightened water retaining ability of thehorny layer and exhibited skin roughness preventive • remedial effects.Compounds (A), (C), (D), (E), (G) and (K) were each excellent inmiscibility and mixing stability.

TABLE 23 (Composition) (%) Diamide compound (A), (C), (D), (E), (G) or(K) 3.0 Cetyloxypropylglyceryl methoxypropyl myristamide (Example 1.0 1of Japanese Patent Laid-Open No. Hei 08-319263) Phytosphingosine(product of cosmoferm) 0.1 Stearic acid 0.2 Palmitic acid 0.3 Lanolinefatty acid cholesterol 0.5 2-Ethylhexyl p-methoxycinnamate 5.0Silicon-coated titanium dioxide 7.0 Silicon-coated zinc oxide 3.0Polyether-modified silicone 2.0 Alkyl-modified silicone 2.0 Cyclicsilicone 15.0 Sodium silicate 1.0 Glycerin 2.0 Dipropylene glycol 3.0Kitin 1.0 Cysteine 0.2 Burnet extract (Maruzen Pharmaceutical Co., Ltd.)0.3 Stearyl glycyrrhizinate 0.2 Methyl paraoxybenzoate q.s. Perfume q.s.Purified water Balance

INDUSTRIAL APPLICABILITY

Diamide derivatives (I) of the present invention penetrate into thelipid layer between horny cells, thereby exerting effects of improving(maintaining • reinforcing) water retention capacity and barrierfunctions of the horny layer or penetrate into the hair, therebyheightening hair protecting effects and at the same time, they have goodsolubility and excellent stability in a base ingredient. Thecompositions for external application, humectants and skin barrierfunction reinforcing agents according to the present invention thereforeexhibit effects in prevention treatment of chapping, anti-aging of theskin, improvement in the touch feel of the hair, and prevention andremedy of the chapping of the scalp and are useful as pharmaceuticals,cosmetics or quasi-drugs excellent in stability. The compositions forexternal application according to the present invention can be preparedefficiently at a low cost.

1. A composition for external application, which comprises a diamidederivative represented by the following formula (1):

(wherein, R^(1a) and R^(1b) are the same or different and eachrepresents a linear C₁₋₂₃ alkyl or C₂₋₂₃ alkenyl group, R^(2a) andR^(2b) are the same or different and each represents a divalent C₁₋₆hydrocarbon group, R³s are the same or different and each represents adivalent C₂₋₆ hydrocarbon group and n stands for 1 to 100).
 2. Acomposition for external application, which comprises a diamidederivative represented by the following formula (1):

(wherein, R^(1a) and R^(1b) are the same or different and eachrepresents a linear C₁₋₂₃ alkyl or C₂₋₂₃ alkenyl group, R^(2a) andR^(2b) are the same or different and each represents a divalent C₁₋₆hydrocarbon group, R³s are the same or different and each represents adivalent C₂₋₆ hydrocarbon group and n stands for 1 to 100) and anintercellular lipid component of the horny layer.
 3. A composition forexternal application according to claim 2 wherein the intracellularlipid component of the horny layer is at least one member selected fromthe group consisting of ceramides, pseudoceramids, sphingoglycolipids,sphingophospholipids, sphingosines and derivatives thereof, sphinganinesand derivatives thereof, higher fatty acids and cholesterols andderivatives thereof.
 4. A humectant, which comprises as an effectiveingredient, a diamide derivative represented by the following formula(1):

(wherein, R^(1a) and R^(1b) are the same or different and eachrepresents a linear C₁₋₂₃ alkyl or C₂₋₂₃ alkenyl group, R^(2a) andR^(2b) are the same or different and each represents a divalent C₁₋₆hydrocarbon group, R³s are the same or different and each represents adivalent C₂₋₆ hydrocarbon group and n stands for 1 to 100).
 5. A skinbarrier function reinforcing agent, which comprises as an effectiveingredient, a diamide derivative represented by the following formula(1):

(wherein, R^(1a) and R^(1b) are the same or different and eachrepresents a linear C₁₋₂₃ alkyl or C₂₋₂₃ alkenyl group, R^(2a) andR^(2b) are the same or different and each represents a divalent C₁₋₆hydrocarbon group, R³s are the same or different and each represents adivalent C₂₋₆ hydrocarbon group and n stands for 1 to 100).
 6. Thecomposition of claim 1, further comprises an oily base.
 7. Thecomposition claim 6, wherein said oily base is at least one memberselected from the group consisting of vegetable oils, animal oils,synthetic oils, fatty acids, natural glycerides and syntheticglycerides.
 8. The composition of claim 1, which comprises 0.001 to 5wt. % of said diamide.
 9. The composition of claim 8, further comprisingan anionic surfactant.
 10. The composition of claim 9, wherein saidanionic surfactant is present in an amount of 5 to 30 wt. %.
 11. Thecomposition of claim 1, which comprises 0.1 to 20 wt. % of said diamide.12. The composition of claim 11, further comprising at least onesurfactant selected from the group consisting of cationic surfactant andnon-ionic surfactant.
 13. The composition of claim 12, wherein saidsurfactant is present in an amount of 0.1 to 50 wt. %.
 14. Thecomposition of claim 1, wherein said composition comprises 0.01 to 5 wt.% of said diamide.
 15. The composition of claim 14, wherein saidcomposition further comprises a nonionic surfactant.
 16. The compositionof claim 15, wherein said nonionic surfactant is present in an amount of0.01 to 20 wt. %.
 17. A composition for external application, whichcomprises a diamide derivative represented by the following formula (1):

(wherein, R^(1a) and R^(1b) are the same or different and eachrepresents a C₁₋₂₃ hydrocarbon group, R^(2a) and R^(2b) are the same ordifferent and each represents a divalent C₁₋₆ hydrocarbon group, R³s arethe same or different and each represents a divalent C₂₋₆ hydrocarbongroup and n stands for 1 to 100); and a non-ionic surfactant whereinsaid diamide derivative is represented by the following formula (C):


18. The composition of claim 17, further comprising an intercellularlipid component of the horny layer.
 19. A composition for externalapplication according to claim 18 wherein the intracellular lipidcomponent of the horny layer is at least one member selected from thegroup consisting of ceramides, pseudoceramids, sphingoglycolipids,sphingophospholipids, sphingosines and derivatives thereof, sphinganinesand derivatives thereof higher fatty acids and cholesterols andderivatives thereof.
 20. The composition of claim 17, further comprisesan oily base.
 21. The composition claim 20, wherein said oily base is atleast one member selected from the group consisting of vegetable oils,animal oils, synthetic oils, fatty acids, natural glycerides andsynthetic glycerides.
 22. The composition of claim 17, which comprises0.1 to 20 wt. % of said diamide.
 23. The composition of claim 22,further comprising a cationic surfactant.
 24. The composition of claim23, wherein said surfactant is present in an amount of 0.1 to 50 wt. %.25. The composition of claim 17, wherein said nonionic surfactant ispresent in an amount of 0.01 to 20 wt. %.
 26. A composition for externalapplication, which comprises a diamide derivative represented by thefollowing formula (1):

(wherein, R^(1a) and R^(1b) are the same or different and eachrepresents a C₁₋₂₃ hydrocarbon group, R^(2a) and R^(2b) are the same ordifferent and each represents a divalent C₁₋₆ hydrocarbon group, R³s arethe same or different and each represents a divalent C₂₋₆ hydrocarbongroup and n stands for 1 to 100); and an organic acid or salt thereofwherein said diamide derivative is represented by the following formula(C):


27. The composition of claim 26, further comprising an intercellularlipid component of the horny layer.
 28. A composition for externalapplication according to claim 27 wherein the intracellular lipidcomponent of the horny layer is at least one member selected from thegroup consisting of ceramides, pseudoceramids, sphingoglycolipids,sphingophospholipids, sphingosines and derivatives thereof, sphinganinesand derivatives thereof, higher fatty acids and cholesterols andderivatives thereof.
 29. The composition of claim 26, further comprisesan oily base.
 30. The composition claim 29, wherein said oily base is atleast one member selected from the group consisting of vegetable oils,animal oils, synthetic oils, fatty acids, natural glycerides andsynthetic glycerides.
 31. The composition of claim 26, which comprises0.001 to 5 wt. % of said diamide.
 32. The composition of claim 31,further comprising an anionic surfactant.
 33. The composition of claim32, wherein said anionic surfactant is present in an amount of 5 to 30wt. %.
 34. The composition of claim 26, which comprises 0.1 to 20 wt. %of said diamide.
 35. The composition of claim 34, further comprising atleast one surfactant selected from the group consisting of cationicsurfactant and non-ionic surfactant.
 36. The composition of claim 35,wherein said surfactant is present in an amount of 0.1 to 50 wt. %. 37.The composition of claim 26, wherein said composition comprises 0.01 to5 wt. % of said diamide.
 38. The composition of claim 37, wherein saidcomposition further comprises a nonionic surfactant.
 39. The compositionof claim 38, wherein said nonionic surfactant is present in an amount of0.01 to 20 wt. %.